Alzheimer and cardiovascular genetic scores and cognition: the FINGER randomized controlled trial

Abstract Alzheimer's disease and coronary artery disease are common late-life chronic conditions and share multiple risk factors, including Apolipoprotein E (APOE) ε4 allele. A meta-analysis of two multidomain lifestyle intervention trials indicated more cognitive benefit in APOE4 carriers compared with non-carriers. This study investigated the impact of genetic risk scores for Alzheimer's disease and coronary artery disease (AD-GRS, CAD-GRS) on cognition in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) randomized controlled trial. FINGER included 1259 at-risk individuals without dementia from the general population, aged 60-77 years. Participants were randomized 1:1 to 2-year multidomain lifestyle intervention or regular health advice. Primary outcome was change in cognition based on a modified Neuropsychological Test Battery (14 tests). Previous comprehensive AD-GRS and CAD-GRS were calculated using GWAS data (1,177 participants with 585 in control and 592 in intervention group, exploratory analysis). The intervention-control difference in annual overall cognition change (95% CI) for participants with AD-GRS above/below the median (i.e., higher/lower risk) was 0·032 (0·002-0·063) versus 0·017 (-0·011- 0·045), and for CAD-GRS above/below the median was 0·031 (0·002-0·059) versus 0·016 (-0·012-0·044). AD-GRS or CAD-GRS were not significantly related to the intervention effect overall (p>0·46), but for AD-GRS there were differences between women and men (p=0·024). The intervention-control difference in annual overall score change was 0·045 (0·004-0·087) for higher-risk women, 0·003 (-0·040-0·047) for lower-risk women, 0·019 (-0·026-0·064) for higher-risk men, and 0·027 (-0·009-0·064) for lower-risk men. People with genetic susceptibility for Alzheimer's disease/dementia or coronary artery disease can benefit from multidomain lifestyle interventions. Although the findings for AD-GRS and CAD-GRS risk groups were similar to APOE4 carrier status, with additional gender differences for AD-GRS, these exploratory findings need to be verified across several multidomain lifestyle trials to ensure adequate statistical power and inclusion of genetically diverse populations.